Ethyl phenylacetate → Ethyl 3-(2-fluoro-4-methylphenyl)-3-oxo-2-phenylpropanoate

HRID 1471924Notes

Reaction equation

HRID 1471924 reaction equation
[C:1]1([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[F:23][C:24]1[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:25]=1[C:26](Cl)=[O:27]>C1COCC1>[F:23][C:24]1[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:25]=1[C:26](=[O:27])[CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

5

Reactant 3

HCID 7590Ethyl phenylacetateHCID 2733832Lithium HexamethyldisilazideHCID 51733672-Fluoro-4-methylbenzoyl chloride

Product 1

HCID 67384741Ethyl 3-(2-fluoro-4-methylphenyl)-3-oxo-2-phenylpropanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The solution of ethyl 2-phenylacetate (5 g, 30.5 mmol) in THF (20 mL) was cooled to −78° C. and LiHMDS (30.5 mL, 30.5 mmol) was added, followed by prior made solution of 2-fluoro-4-methylbenzoyl chloride in THF (10 mL). The reaction was allowed to warm to room temperature slowly and stirred for 4 h. Quenched with AcOH (2 mL), extracted with EtOAc, washed with brine, dried over MgSO4, and purified by column chromatography to give the title compound as clear liquid (7.10 g). LCMS m/z=301.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (t, J=7.07 Hz, 3H), 2.32 (s, 3H), 4.22 (q, J=7.07 Hz, 2H), 5.77 (s, 1H), 7.03-7.17 (m, 3H), 7.24-7.40 (m, 4H), 7.82 (t, J=8.21 Hz, 1H).

Workup

  1. customQuenched with AcOH (2 mL)
  2. extractionextracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-9e56218e5d9f451aa06de5aa9b6de36c
Source dataset
uspto-grants-2015_04
Patent number
US09012478B2

Reaction notes

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